Anxiety & Depression Association of America

for Participant: 1. Male and female patients 18 to 75 years old, inclusive. 2. Patients who can read, understand, and provide written informed consent. 3. Patients who meet the Diagnostic and Statistical Manual of Mental Disorders, v5, Text Revision (DSM-5-TR) criteria for a primary diagnosis of bipolar I or bipolar II disorder, schizophrenia, schizoaffective or schizophreniform disorder. 4. Patients who, in the opinion of the principal investigator, are in good general health prior to study participation as determined by a detailed medical history, a physical examination, and a 12-lead electrocardiogram (ECG). 5. Female participants, if of child-bearing potential and sexually active, and male participants, if sexually active with a partner of child-bearing potential, agree to use a medically acceptable and effective birth control method throughout the study and for one month following the end of the study. 6. Based on history, in the past 30 days prior to Screening, patients must have had at least one clinical presentation of agitation requiring intervention. 7. Patients who are receiving stable psychotropic treatment for 30 days prior to Screening for the underlying primary diagnosis and who are expected to remain on stable treatment for the duration of the study. Inclusion Criteria for Informant: 1. At least 18 years of age at the time of screening. 2. Is a spouse, significant other, family member, friend, home health aide, or residence manager of an adult patient who: 1. Has a clinical diagnosis of bipolar I or bipolar II disorder, schizophrenia, schizoaffective or schizophreniform disorder. 2. Is determined to be eligible for the study per the patient inclusion/exclusion criteria. 3. Has known the patient for at least 12 months cumulatively. 4. Currently living with or routinely contacting the patient at least five days a week. 5. Does not plan to discontinue contact with the patient during the study period. 6. Willing and able to provide written informed consent.

for Participant: 1. Patients with serious or unstable medical illnesses. These include current hepatic (moderate-severe hepatic impairment), renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease, congestive heart failure), endocrinologic, or hematologic disease. 2. Psychiatric comorbidities are generally allowed; however, moderate or severe substance use disorders (SUD) (within the past 6 months) are exclusionary if the substance involved is other than nicotine or caffeine. 3. The investigator believes the patient has a history of agitation episodes due to substance use. 4. A diagnosis of antisocial personality disorder, borderline personality disorder, or narcissistic personality disorder that predated the diagnosis of schizophrenia or bipolar disorder, or in the opinion of the Investigator, is independent of the signs and symptoms of the schizophrenia or bipolar disorder. 5. Suicidality as assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Clinically significant risk of suicide based on the Investigator's clinical opinion or a history of an actual suicide attempt in the last year are also exclusionary. 6. Female patients who have a positive pregnancy test at screening/baseline or are breastfeeding. 7. Currently treated with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin), alpha-2 adrenergic agonists, or other prohibited medications. 8. Patients with hydrocephalus, seizure disorder, or history of significant head trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor, encephalopathy, meningitis, Parkinson's disease, or focal neurological findings. 9. Patients with ECG abnormalities considered clinically significant by the Investigator or qualified designee with clinical implications for the patient's participation in the study. 10. Patients who have received an investigational drug within 30 days prior to Baseline. 11. For any reason, patients considered by the Investigator, or designee, to be unsuitable candidates for receiving dexmedetomidine, e.g., patients with a history of allergic reactions to dexmedetomidine. Exclusion Criteria for Informant: 1. Appears to have an impairment (e.g., cognitive, hearing, visual) or insufficient knowledge of the English language that could interfere with their ability to provide written consent, complete written assessments, or an interview (based on screener judgment). 2. Unable to accompany the patient and remain present at the clinical site to complete ratings for the full two-hour data collection period while the patient experiences an acute agitation episode that needs to be treated.